In dryland river catchments, palaeochannels provide some of the key records for understanding the changes in river character and behaviour that can occur in response to different extrinsic and intrinsic controls. Here, we combine modern hydroclimatic datasets, satellite imagery, field surveys, and optically stimulated luminescence (OSL) dating of palaeochannels to investigate the response of the ~850 km long Warrego River, located in central eastern Australia, to Holocene hydroclimatic change. The modern Warrego is an intermittent to ephemeral, low energy river (unit stream power, ω, ≤4 W m−2), and is characterised by low sinuosity (‘straight’), narrow (<50 m), single-thread, anabranching, and distributary channels that transport fine-grained (dominantly mud and sand) sediment. Marked downstream declines in discharge and stream power mean that many channels are discontinuous, terminating downstream at floodouts or in unchannelled floodplain wetlands before reaching the Darling River. By contrast, OSL ages and palaeohydrological reconstructions show that between ~8 and 5 ka, higher energy (~8–10 W m−2), wider (~160 m), meandering channels were the characteristic river style. In the Burrenbilla and Coongoola palaeochannels, prevailing La Niña conditions were likely responsible for bankfull discharges between 3 and 59 times those of the modern river, which probably enabled the palaeochannels to maintain perennial flow in continuous courses to the Darling River. After ~5 ka, El Niño events became stronger and more frequent, leading to greater catchment aridity and lower, more variable, river discharges. These extrinsic changes resulted in intrinsic adjustments to river character and behaviour, with key geomorphic thresholds being crossed in the cessation of meandering and establishment of the modern single-thread, anabranching, and distributary channels. The Warrego River's dramatic pattern transformation in response to mid- to late Holocene hydroclimatic change has similarities with some other Australian dryland river responses over equivalent timeframes. The pattern transformation demonstrates the Warrego River's sensitivity to extrinsic forcing and represents one of the most profound dryland river changes in the late Quaternary.